A conserved sequence in the immunoglobulin J kappa-C kappa intron: possible enhancer element

Several functionally important genetic elements (such as the TATA box, mRNA splice sequences, poly(A) addition signal) were first detected as short segments of unexplained sequence homology within non-coding regions of different genes. A short region of unknown sequence in the intron between the human J kappa and C kappa immunoglobulin coding regions was found to be sufficiently homologous to the corresponding segment of the mouse gene to form stable heteroduplexes. Although no specific function has yet been definitely ascribed to this region (which we call the kappa intron conserved region, or KICR), some functional significance has been inferred from the findings that (1) activation of B lymphocytes induces a DNase hypersensitivity site in this region and (2) deletions including this region reduce expression of kappa genes introduced into lymphoid cells. To delineate the KICR more precisely and to test the generality of the sequence conservation in a third species, we have sequenced this region of the human and mouse genes and have examined the corresponding region of a recently cloned rabbit kappa gene. We find a segment of about 130 base pairs (bp) that shows striking conservation in all three species, demonstrating homology significantly higher than within the C kappa coding region itself. Two short sequences from the J kappa-C kappa intron that were noted by other investigators to be homologous to proposed 'enhancer' sequences both lie within the conserved region.     

Racemic amino acids from the ultraviolet photolysis of interstellar ice analogues

The delivery of extraterrestrial organic molecules to Earth by meteorites may have been important for the origin and early evolution of life. Indigenous amino acids have been found in meteorites-over 70 in the Murchison meteorite alone. Although it has been generally accepted that the meteoritic amino acids formed in liquid water on a parent body, the water in the Murchison meteorite is depleted in deuterium relative to the indigenous organic acids. Moreover, the meteoritical evidence for an excess of laevo-rotatory amino acids is hard to understand in the context of liquid-water reactions on meteorite parent bodies. Here we report a laboratory demonstration that glycine, alanine and serine naturally form from ultraviolet photolysis of the analogues of icy interstellar grains. Such amino acids would naturally have a deuterium excess similar to that seen in interstellar molecular clouds, and the formation process could also result in enantiomeric excesses if the incident radiation is circularly polarized. These results suggest that at least some meteoritic amino acids are the result of interstellar photochemistry, rather than formation in liquid water on an early Solar System body.     

Trace element signature of subduction-zone fluids, melts and supercritical liquids at 120-180 km depth

Fluids and melts liberated from subducting oceanic crust recycle lithophile elements back into the mantle wedge, facilitate melting and ultimately lead to prolific subduction-zone arc volcanism. The nature and composition of the mobile phases generated in the subducting slab at high pressures have, however, remained largely unknown. Here we report direct LA-ICPMS measurements of the composition of fluids and melts equilibrated with a basaltic eclogite at pressures equivalent to depths in the Earth of 120-180 km and temperatures of 700-1,200 degrees C. The resultant liquid/mineral partition coefficients constrain the recycling rates of key elements. The dichotomy of dehydration versus melting at 120 km depth is expressed through contrasting behaviour of many trace elements (U/Th, Sr, Ba, Be and the light rare-earth elements). At pressures equivalent to 180 km depth, however, a supercritical liquid with melt-like solubilities for the investigated trace elements is observed, even at low temperatures. This mobilizes most of the key trace elements (except the heavy rare-earth elements, Y and Sc) and thus limits fluid-phase transfer of geochemical signatures in subduction zones to pressures less than 6 GPa.     

Variations in earthquake-size distribution across different stress regimes

The earthquake size distribution follows, in most instances, a power law, with the slope of this power law, the 'b value', commonly used to describe the relative occurrence of large and small events (a high b value indicates a larger proportion of small earthquakes, and vice versa). Statistically significant variations of b values have been measured in laboratory experiments, mines and various tectonic regimes such as subducting slabs, near magma chambers, along fault zones and in aftershock zones. However, it has remained uncertain whether these differences are due to differing stress regimes, as it was questionable that samples in small volumes (such as in laboratory specimens, mines and the shallow Earth's crust) are representative of earthquakes in general. Given the lack of physical understanding of these differences, the observation that b values approach the constant 1 if large volumes are sampled was interpreted to indicate that b = 1 is a universal constant for earthquakes in general. Here we show that the b value varies systematically for different styles of faulting. We find that normal faulting events have the highest b values, thrust events the lowest and strike-slip events intermediate values. Given that thrust faults tend to be under higher stress than normal faults we infer that the b value acts as a stress meter that depends inversely on differential stress.     

DNA repair protein Ku80 suppresses chromosomal aberrations and malignant transformation

Cancer susceptibility genes have been classified into two groups: gatekeepers and caretakers. Gatekeepers are genes that control cell proliferation and death, whereas caretakers are DNA repair genes whose inactivation leads to genetic instability. Abrogation of both caretaker and gatekeeper function markedly increases cancer susceptibility. Although the importance of Ku80 in DNA double-strand break repair is well established, neither Ku80 nor other components of the non-homologous end-joining pathway are known to have a caretaker role in maintaining genomic stability. Here we show that mouse cells deficient for Ku80 display a marked increase in chromosomal aberrations, including breakage, translocations and aneuploidy. Despite the observed chromosome instabilities, Ku80-/- mice have only a slightly earlier onset of cancer. Loss of p53 synergizes with Ku80 to promote tumorigenesis such that all Ku80-/- p53-/- mice succumb to disseminated pro-B-cell lymphoma before three months of age. Tumours result from a specific set of chromosomal translocations and gene amplifications involving IgH and c-Myc, reminiscent of Burkitt's lymphoma. We conclude that Ku80 is a caretaker gene that maintains the integrity of the genome by a mechanism involving the suppression of chromosomal rearrangements.     

Generation of Fock states in a superconducting quantum circuit

Spin systems and harmonic oscillators comprise two archetypes in quantum mechanics. The spin-1/2 system, with two quantum energy levels, is essentially the most nonlinear system found in nature, whereas the harmonic oscillator represents the most linear, with an infinite number of evenly spaced quantum levels. A significant difference between these systems is that a two-level spin can be prepared in an arbitrary quantum state using classical excitations, whereas classical excitations applied to an oscillator generate a coherent state, nearly indistinguishable from a classical state. Quantum behaviour in an oscillator is most obvious in Fock states, which are states with specific numbers of energy quanta, but such states are hard to create. Here we demonstrate the controlled generation of multi-photon Fock states in a solid-state system. We use a superconducting phase qubit, which is a close approximation to a two-level spin system, coupled to a microwave resonator, which acts as a harmonic oscillator, to prepare and analyse pure Fock states with up to six photons. We contrast the Fock states with coherent states generated using classical pulses applied directly to the resonator.     

Tricellulin forms homomeric and heteromeric tight junctional complexes

Sealing of the paracellular cleft by tight junctions is of central importance for epithelia and endothelia to function as efficient barriers between the extracellular space and the inner milieu. Occludin and claudins represent the major tight junction components involved in establishing this barrier function. A special situation emerges at sites where three cells join together. Tricellulin, a recently identified tetraspan protein concentrated at tricellular contacts, was reported to organize tricellular as well as bicellular tight junctions. Here we show that in MDCK cells, the tricellulin C-terminus is important for the basolateral translocation of tricellulin, whereas the N-terminal domain appears to be involved in directing tricellulin to tricellular contacts. In this respect, identification of homomeric tricellulin-tricellulin and of heteromeric tricellulin-occludin complexes extends a previously published model and suggests that tricellulin and occludin are transported together to the edges of elongating bicellular junctions and get separated when tricellular contacts are formed.     

Erythropoietin modulates the neural control of hypoxic ventilation

Numerous factors involved in general homeostasis are able to modulate ventilation. Classically, this comprises several kind of molecules, including neurotransmitters and steroids that are necessary for fine tuning ventilation under different conditions such as sleep, exercise, and acclimatization to high altitude. Recently, however, we have found that erythropoietin (Epo), the main regulator of red blood cell production, influences both central (brainstem) and peripheral (carotid bodies) respiratory centers when the organism is exposed to hypoxic conditions. Here, we summarize the effect of Epo on the respiratory control in mammals and highlight the potential implication of Epo in the ventilatory acclimatization to high altitude, as well as in the several respiratory sickness and syndromes occurring at low and high altitude. (Part of a multi-author review.)